Epitopes described in "Immunology of Diabetes Society T-Cell Workshop: HLA class I tetramer-directed epitope validation initiative T-Cell Workshop Report-HLA Class I Tetramer Validation Initiative."

Article Authors:R Mallone; M Scotto; C N Janicki; E A James; L Fitzgerald-Miller; R Wagner; P Gottlieb; J Thorpe; N Jospe; I Durinovic-Bellò; C Boitard; O Lou; C M Dayan; F S Wong; T-Cell Workshop Committee, Immunology of Diabetes Society
Article Title:Immunology of Diabetes Society T-Cell Workshop: HLA class I tetramer-directed epitope validation initiative T-Cell Workshop Report-HLA Class I Tetramer Validation Initiative.
Reference Detail
Reference ID:1022561
Abstract:BACKGROUND: Identification of T-cell reactivity to -cell antigen epitopes is an important goal for studying pathogenesis and for designing and monitoring of immunotherapeutic interventions in type 1 diabetes (T1D). METHODS: We performed a multicentre validation of known human leukocyte antigen (HLA) class I CD8+ T-cell epitopes. To this end, peripheral blood T-cell responses were measured in 35 recently (<2 years) diagnosed HLA-A*02:01+ T1D patients using blind-coded HLA-A2 tetramers (TMrs) and pentamers (PMrs), encompassing two epitopes of preproinsulin (PPI; PPIA12-20 and PPIB10-18) and two epitopes of glutamic acid decarboxylase (GAD; GAD114-122 and GAD536-545). We also compared the readout of TMrs and PMrs with a CD8+ T-cell interferon- enzyme-linked immunospot assay. RESULTS: Despite the minute frequencies of autoreactive cells detected by TMrs/PMrs, most (73-77%) T1D patients had responses to one or more of the epitopes used. All four epitopes were recognized by T1D patients, with a prevalence ranging from 5 to 25%. TMrs and PMrs detected more positive responses to the -cell epitopes than CD8+ T-cell interferon- enzyme-linked immunospot. However, concordance between positive responses to TMrs and PMrs was limited. CONCLUSIONS: Using a multicentre blind-coded setup and three different T-cell assays, we have validated PPI and GAD epitopes as commonly recognized CD8+ T-cell targets in recently diagnosed T1D patients. Both TMrs and PMrs showed higher detection sensitivity than the CD8+ T-cell interferon- enzyme-linked immunospot assay. However, there are some important methodological issues that need to be addressed in using these sensitive techniques for detecting low frequency responses.
Affiliations:INSERM U986, DeAR Lab Avenir, Saint Vincent de Paul Hospital, and Paris Descartes University, Paris, France. Roberto.Mallone@inserm.fr
Reference Type:Literature
PubMed ID:22069251
Journal:Diabetes Metab Res Rev
Journal Volume:27
Article Pages:720-6
Journal ISSN:1520-7552
Article Chemical List:Epitopes, T-Lymphocyte;HLA-A Antigens;Histocompatibility Antigens Class I;Insulin;Protein Precursors;preproinsulin;Interferon-gamma;Glutamate Decarboxylase
Article MeSH List:Adolescent; Adult; CD8-Positive T-Lymphocytes(immunology); Diabetes Mellitus, Type 1(immunology); Enzyme-Linked Immunospot Assay; Epitopes, T-Lymphocyte(immunology); Glutamate Decarboxylase(immunology); HLA-A Antigens(immunology); Histocompatibility Antigens Class I(immunology); Humans; Insulin(immunology); Interferon-gamma(immunology); Protein Precursors(immunology)
Curation Last Updated:2014-10-03 22:30:52